Correlation analysis of DDR and SWI/SNF gene mutation and the efficacy of immune checkpoint inhibitors in solid tumors.
Authors: Da Jiang, Minhui Shi, Hui Zhang, Yanzhi Cui, Lei Hong, Ying Li, Fang Huang, Xue Zhang, Wenya Song, Ruoying Deng
Journal: Journal of Clinical Oncology (2022)

e14603 Background: To investigate whether DDR and SWI/SNF gene mutation can predict the efficacy of immune checkpoint inhibitors (ICIs) in malignant solid tumors. Methods: A total of 113 patients with malignant solid tumors proven for distant metastasis or infeasible surgery pathologically were included in this study, all of whom were treated with ICIs and tested for genes by Next Generation Sequencing (≥150 genes). The basic clinical characteristics, gene variations and the efficacy of ICIs of these patients were retrospectively collected and statistically analyzed. Results: It’s about 21 kinds of tumors in these patients, including 58 patients with lung cancer (49 patients with non-small cell lung cancer) and 28 patients with digestive system cancer. The median follow-up time was 4.3 months (0.5m to 37.9m). A total of 46 DDR genes and 7 SWI/SNF genes were screened out, the probability of DDR gene mutation was 52.21% (59/113) and SWI/SNF gene was 25.66% (29/113). TMB-H was correlated with DDR and SWI/SNF gene mutation ( P= 0.001, P= 0.043). Patients with TMB-H had a higher ORR than the Non TMB-H patients (47.37% vs 16.67%, P= 0.008, OR= 4.500, 95% CI = 1.484-13.642). The ORR of patients with strong positive PD-L1 was higher than the patients with weak positive and negative PD-L1 (58.33% vs 16.67%, P= 0.024, OR= 7.000, 95% CI = 1.293-37.909; 58.33% vs 22.86%, P = 0.029, OR = 4.725, 95% CI = 1.174-19.021). The ORR of DDR gene mutation patients was higher than the wild-type patients (35.29% vs 11.11%, P= 0.008, OR= 4.364, 95% CI = 1.463-13.015). Compared with wild-type patients, the ORR of SWI/SNF gene mutation patients showed an increased trend (37.04% vs 18.84%, P= 0.065, OR= 2.534, 95% CI = 0.944-6.799). The ORR was higher in patients with DDR and SWI/SNF gene co-mutation than the wild-type patients (50.00% vs 11.11%, P= 0.003, OR= 8.000, 95% CI= 1.991-32.142) and the patients with DDR or SWI/SNF gene single mutation alone (50.00% vs 23.81%, P= 0.050, OR= 3.200, 95% CI = 0.998-10.262).After excluding the effect of TMB, DDR gene mutation, DDR and SWI/SNF gene co-mutation still had statistical differences ( P= 0.020, P= 0.012). The mPFS of DDR or SWI/SNF gene mutation patients were significantly higher than the wild-type patients (7.1m vs 5.7m, HR= 0.828, 95% CI = 0.500-1.372, P= 0.464; 7.4m vs 5.7m, HR = 0.729, 95% CI = 0.412-1.291, P = 0.279). The mPFS of DDR and SWI/SNF gene co-mutation patients was higher than the single mutation and wild-type patients (9.4m vs 4.3m, HR= 0.644, 95% CI = 0.332-1.251, P= 0.211; 9.4m vs 5.7m, HR= 0.615, 95% CI = 0.291-1.298, P= 0.202), but there was no statistical difference. Conclusions: The ORR and mPFS of patients with DDR or SWI/SNF gene mutation were better than the wild-type patients in Immunotherapy, especially those patients with DDR and SWI/SNF gene co-mutation. Therefore, the detection of these two groups of genes may be helpful to screen the beneficial patients to ICIs.